Several lines of evidence have suggested that hormonal exposures early in life, including those in-utero, may influence the risk of breast and other hormonally related tumors in adults. Several studies are underway to assess this. We have reassembled U.S.-based cohorts of diethylstilbestrol (DES)-exposed daughters, sons and mothers that had been studied in the 1970s and 1980s. We have conducted two combined follow-up efforts (1994 and 1998) covering approximately 3,600 exposed and 3,500 unexposed mothers, 4,500 exposed and 1,500 unexposed daughters, and 1,800 exposed and 1,600 unexposed sons. A third follow-up was begun in 2001. In addition, two other cohorts have been assembled, one consists of maternal and cord blood samples from pre-eclamptic pregnancies and matching normal pregnancies. The intent is to assess hormonal and other differences that might be responsible for the protective effect of pre-eclampsia on subsequent breast cancer risk. Finally, we have obtained cord blood samples from normal pregnancies in China and the U.S., and will be comparing hormonal and growth factor levels between the two populations to assess differences that might relate to the population differences in breast cancer risk. Among the DES exposed, mothers have a significant 30% excess risk of breast cancer, with other cancers occuring at about expected levels; DES daughaters have a 40-fold excess risk of clear-cell adenocarcinoma of the vagina and a 2-fold excess risk of squamous dysplasia of the cervix. Thus far, exposed sons have shown no excesses, except for a non-statistically significant excess of germ-cell malignancies, primarily of the testes. In conjunction with this year's follow-up we will also be attempting to assemble a grandaughters' cohort (offspring of DES exposed daughters). Preliminary analyses have found no differences in estrogen levels in blood of pre-eclamptic mothers versus those with a normal pregnancy, but have documented an increase in circulating androgens. Cord bloods from Asian and U.S. pregnancies have been obtained and arrangements are now being made for laboratory analyses.